Reactive arthritis has been found to result from gastrointestinal infections with Yersinia enterocolitica, Salmonella, Shigella, and Campylobacter and from genital tract infections with Chlamydia trachomatis. Despite a knowledge of the association of these bacteria with reactive arthritis, little is known of the mechanism by which the arthropathy develops. It is the objective of this proposal to investigate the mechanisms by which reactive arthritis develops as a consequence of genital infections with Chlamydia trachomatis. An understanding of these mechanisms may help to recognize susceptible patients and to develop prophylactic strategies. These studies will be conducted in a murine model of reactive arthritis which is produced by inoculating inactivated chlamydial antigen into mice which have been infected genitally with the agent of mouse pneumonitis (MoPn), a C. trachomatis biovar. An immune response to the offending bacterium has been implicated in humans as being a prerequisite for the production of arthritis. In the mouse model, previous studies have indicated that cell mediated immunity is the effector mechanism; thus, this study will characterize the T cell subpopulations which are required. This will be accomplished by separation of the populations and adoptive transfer into naive mice in which antigen will be inoculated intra-articularly. The role of antibody and T suppressor cells will be investigated using antibody and adoptive cell transfer systems. The nature of the chlamydial antigen responsible for eliciting the arthritis will be determined by challenging MoPn-infected animals in the joint with different chlamydial serovars and species, other arthritis-inducing bacteria, and purified outer membrane components of chlamydiae. Potential cross-reactivity of chlamydial antigens with host joint antigens will also be studied. Finally, strains of mice bearing different H-2 antigens will be assessed for their arthritic potential to determine if there is a relationship with histocompatibility antigens as occurs in humans.